Glutamine has beneficial effects on enterocytes and the immune system in sepsis, but its effects on hepatic metabolism remain unknown. The aim of the present study was to determine the effects of glutamine on hepatocyte energy metabolism under conditions of neonatal endotoxaemia. Suckling Wistar rats were injected intraperitoneally with 200μg/kg lipopolysaccharide. Oxygen consumption was measured polarographically in hepatocytes respiring on either palmitate (0.5mM) or palmitate plus glutamine (10mM). Total hepatocyte oxygen consumption was similar in hepatocytes from control and endotoxic rats, but this was due to a decrease in intramitochondrial and an increase in extramitochondrial oxygen consumption in the cells from endotoxic animals. The addition of glutamine to hepatocytes from endotoxic rats restored intramitochondrial oxygen consumption to control levels. Although glutamine did not reverse the inhibition of the thermogenic proton leak observed in endotoxaemia, it significantly increased oxygen consumption due to mitochondrial ATP synthesis (P = 0.03). Glutamine significantly increased the hepatocyte ATP/ADP ratio (P = 0.02 compared with hepatocytes from endotoxic rats). Electron microscopy revealed morphological damage to the mitochondria of hepatocytes from endotoxic rats, and a return to a normal appearance with the addition of glutamine. We conclude that glutamine reverses the inhibition of mitochondrial metabolism that is observed in endotoxaemia. The effect is primarily at the level of ATP synthesis.
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February 15 2002
Hepatocyte mitochondrial metabolism is inhibited in neonatal rat endotoxaemia: effects of glutamine
Michele A. MARKLEY;
Michele A. MARKLEY
1Department of Paediatric Surgery, Institute of Child Health and Great Ormond Street Hospital for Children, 30 Guilford Street, London WC1N 1EH, U.K.
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Agostino PIERRO;
Agostino PIERRO
1Department of Paediatric Surgery, Institute of Child Health and Great Ormond Street Hospital for Children, 30 Guilford Street, London WC1N 1EH, U.K.
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Simon EATON
1Department of Paediatric Surgery, Institute of Child Health and Great Ormond Street Hospital for Children, 30 Guilford Street, London WC1N 1EH, U.K.
Correspondence: Dr Simon Eaton (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
June 07 2001
Accepted:
November 12 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2002
2002
Clin Sci (Lond) (2002) 102 (3): 337–344.
Article history
Received:
June 07 2001
Accepted:
November 12 2001
Citation
Michele A. MARKLEY, Agostino PIERRO, Simon EATON; Hepatocyte mitochondrial metabolism is inhibited in neonatal rat endotoxaemia: effects of glutamine. Clin Sci (Lond) 1 March 2002; 102 (3): 337–344. doi: https://doi.org/10.1042/cs1020337
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